anion binding: from supramolecules to sensors · phosphate anions through cell membranes is also...

Chem. Listy 93, 546 - 553 (1999) Referáty

ANION BINDING: FROM SUPRAMOLECULES TO SENSORS

VLADIMÍR KRÁL, OLEKSANDR RUSIN,TATIANA SHISHKANOVA, RADKO VOLF,PAVEL MATĚJKA, and KAREL VOLKA

Department of Analytical Chemistry, Institute of ChemicalTechnology, Technická 5, 166 28 Prague 6

Received October 8, 1998

Key wordsxomplexation host-guest, anionic receptors, anio-nic sensors

Natural anion binding receptors (proteins)

It is commonly understood that anions are highly impor-tant compounds in the living cycle of cell. Their influence oncellular biological processes is usually effected via macro-molecular receptors, which are of protein nátuře. Anion-pro-tein complex triggers a number of further biochemical trans-formations. In biological systems, the protein-anion inter-actions serve specific purposes, for example enzymatictransformations (where majority of enzymes bind anions aseither substrates or cofactors), substance transportation, orsignál transduction. They are usually noncovalent in nature.The high specificity of binding of anions to the respectiveligands (proteins) is due to a recognition site in which anionis completely desolvated and bound exclusively via hydrogenbonds. Furthermore, a so-called macrodipole effect, caused byorientation of amino terminus of the protein backbones to-wards the negative guests, contributes to the stability of thecomplex. Then the oppositely charged functional groups of theprotein and anions are paired, and lipophilic groups of theligand display hydrophobic pockets formed by side chains ofthe hydrophobic amino acids . The known anion bindingproteins differ in structure, biochemical functions, and mecha-nisms of complex formation. The guanidinium group presentin the side chain of arginine is ubiquitous in enzymes that bind

anionic substrates and also involved in stabilization of proteintertiary structures via internal salt bridges with carboxylatefunctions . This motif is realized in phosphatases and phos-phorylases, which selectively bind phosphate, as well as indecarboxylases, dehydrogenases, isomerases, and in someproteases, that bind carboxylates. An analogous peculiarity isconnected with the binding site structure of regulátor proteins,the genes expression regulating factors; they bind with a highselectivity the certain sequences of nucleotides in DNA (Fig. 1).

Positively charged groups on the surface of nucleoproteins,the histones, are also capable to form strong (but not sequencespecific) complex with such natural polyanion as DNA.

Some proteins contain metal cations (námely Zn(Il), Fe(II),Mg(II), Ca(II)) in their anion binding sites. Such metal-con-taining proteins (metalloenzymes) form anion complexes asLewis acid hosts, and exhibit selective binding with oxoanions(carboxypeptidases) or small inorganic anions, like O2 (super-oxide dismutase), HCO"3 (carboanhydrase), Cl" and H" (iono-phores and cytochromes). Metal ions, as a Zn2 +, Mg2+, Mn2 +,Ca play decisive role not only in binding anionic substrates,but also in the structure enforcement and all steric switching2.

Anion binding by proteins can be achieved also by hydro-gen-bonding and ion-dipole interactions, especially in theaqueous contents of the cell. A shining example can servesulfáte- and phosphate-binding proteins a. The X-ray crystalstructure showed that this anion was buried deep in the interiorof the protein with the help of seven dedicated hydrogenbonds. There appears to be no functional group present in thebinding cavity that could act as a hydrogen bond acceptor asrequired for binding of these anions.The transport of sulfáte orphosphate anions through cell membranes is also regulated byneutral anion binding proteins .

Artifícial anion binding receptors

Recognition of anionic species has attracted the attentionof many research groups. Research on the supramolecularchemistry of anions (selective recognition of guest moleculesby synthetic receptors) has accelerated in recent years . Thedesign of host molecules for recognizing physiologically im-portant anions, such as carboxylic acids or nucleotides, in

Fig. 1. Adenosine triphosphate (ATP)is a biologically important anion Fig. 2. Positively charged polyaza receptors for halide anions

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aqueous solution is an important in view of the biologicalrelevance of studies in this solvent .

All the known hosts háve been categorized, according totheir primary binding principles, into the positively chargedand the electroneutral species. In this aspect, the extensivefamily of host molecules has been divided into three biggroups. The first one comprises the positively charged anionhosts (Fig. 2).

The overwhelming majority of host compounds of thisgroup are based on cationic nitrogen compounds. There area few examples which suggest complexation by carbenium--based, iodinium, or sulfonium structures2. For this reasonsuch well-known azonia compounds as different azamacrocy-cles (azacrown ethers and cryptands) are described. The bind-ing of an anion by a crown ether can be improved by introduc-tion of positive charges in the ligand. Positive charge can beintroduced onto neutral crown ethers in two ways: either byprotonation of nitrogen donor or complexation by metal ions .Various derivatives of protonated azamacrocycles háve shownhost-guest binding effect with oxalate, sulfáte, fumarate, cit-ráte and some biologically important anions such as AMP ",ADP3", ATP4". Due to their ability to bind phosphate anions,the protonated polyamine azacrown ethers can be ušed to bindnucleotides (ATP", ADP3" and AMP2"). Some of these crownethers (oxaazacrown ethers) were shown to cleave phosphoricanhydrides (ATP-ase activity)2. Several authors reported cer-tain characteristic features of true enzymes which can besuccessfully modeled (catalytic turnover, saturation, and inhi-bition kinetics). With the aim of utilizing these macrocyclesfor ion sensing or membráně transport, they were attached topolystyrene resin or provided with C 1 6 hydrocarbon chains .

Such biologically important linear polyamines as sper-mine and spermidine also belong to this group of receptors.They are capable to bind phosphate and polyanions in waterat neutral pH values. Their analogues, monocyclic hexamines,were designed to recognize dicarboxylic acid anions, and toshow binding activity in aqueous media.

Further progress in the development of new azamacrocy-cles concerned the increase of their selectivity via covalentconnection of two polyammonium macrocycles (assumingtheir cooperative action in anion binding), and rigidization ofbinding sites (bicyclic cryptates)" a 'c. This routě led to theformation of host molecules with augmented binding selecti-vity towards chloride, nitráte, phosphate and citráte anions inaqueous media. Another extension of utilization of water-solu-ble polyaza hosts series consisted in creating of their quater-nary ammonium salts . The anion binding using protonatedpolyaza hosts is severely hampered by the restriction to highlyacidic pH regions, undermining thus any study involving themore basic anions. In addition, switch of the solvent may shiftthe pKa values and thus diminish the total charge by deproto-nation, affecting thereby anion complexation . Nitrogen qua-ternization might offer a remedy in this problém, and indeedthe quaternary ammonium compounds were freely soluble inwater without detectable aggregation and proved to be hostsfor a broad variety of anions in water2. It is interesting, thatsome of these compounds were able to mimic in many respectsthe true enzymes (chemo- and substráte selectivity, saturationkinetics, inhibition, cooperativity, and turnover) . The quater-nary ammonium inclusion hosts are chemically rather stablecompounds and opened the option to study reacting systems

depending on host-guest binding without interference from pHeffects.

Cationic cyclophanes3a are another example of hosts (Fig. 3).The generál binding principle for these anionic guests in

water consist of a superposition of the hydrophobic effect andelectrostatic attractions . Such polyammonium macrocyclesbehave as efficient receptors for polycharged anions in aque-ous solution5. In this čase, preorganization of the macrocyclichost and the spatial charge matching háve been recognized asprimary conditions for strong host-guest interactions. In addi-tion to charge-charge interactions, stacking, solvotropic forcesand hydrogen bonds between anionic species and polyaminereceptors can furnish additional contributions to complex sta-bilization5. Věry strong and selective binding of anions con-taining a combination of hydrophobic and charged moieties aspresent in many biologically important guests, can be expectedfrom the design of cyclophanes satisfying both binding re-quirements. This binding motif, when built into the cyclo-phane framework, provided a series of host compounds capa-ble of binding nucleotides in water. Thus, for instance, theacridinium and phenanťhridinium cyclophanes formed com-plexes in water with nucleotides and planar aromatic carboxy-lates2.

Similar-type polycyclic cyclophanes were prepared from1,3,5-trisubstituted benzenes with carbon chains containingsecondary amines3a These compounds can be solubilized inwater by protonation, and formed complexes with numeroussmall inorganic anions such as nitráte, chloride, and sulfáte.An interesting modification of cyclophanes on the basis ofdiazabicyclooctane and a further quaternization with hydro-phobic moieties formed complexes with nucleotide triphos-phates, and was capable of extracting ATP from a very diluteaqueous solution into the organic phase . Their use in mem-brane transport experiments was not successful, as the deter-genic properties of macrocycle led to disruption of liposomevesicles2.

Side by side with azonia compounds, such positivelycharged anion hosts as oligopyrrole-derived receptors arewidely known. Prominent examples among compounds of thisfamily are polypyrrole complexes like metalloporphyrins andcorrins. The anion-binding capacity of porphyrins depends onthe presence of the metal ion. Small size of porphyrin cavitydoes not allow the use of N-H dipoles for anion stabilization.Expansion of the porphyrin cavity by the incorporation ofmore pyrrolic or other spacer moieties thus appeared as a ratio-nal remedy. A large number of ring-expanded porphyrins in-cluding the sapphyrins, were shown to possess anion-bindingproperties6"12 (Fig. 4).

Diprotonated sapphyrin forms a very stable complex withfluoride, and with oxoanions such as phosphate it may formchelaton-type complex " . Open-chain and cyclic porphyrin

Fig. 3. A positively charged host for hydrophobic anion binding

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dimers bearing various bisamide spacers (1,3-bisamidopro-pane, (l-S^S^-l^-bisamidocyclohexane and (5)-2,2'-bisami-do-1,1' -binaphthalene) were shown to display excellent chiralrecognition properties for aspartate and glutamate anions .Sapphyrin covalently linked to a solid matrix is useful in theseparation of nucleotides, which allows for applying it inaffinity chromatography. Even more promising applicationmay derive from the ability of this compound to bind to single-or double-stranded DNA1 3.

Various other modifications of porphyrins were also de-scribed. For instance, the porphyrins where two pyrrole ringswere replaced by a rigid anthracene spacer, háve a wide-ned cavity, and are capable of more stronger complexationof halides . In another čase, using three porphyrin molecu-les as a building block, a giant cage molecule was obtained,which formed hexaprotonated cations with acids, and hetero-polycluster anions such as [PW12O4{)]

3", [SiW1 2O4 0]4" and[Os10C(CO)24] ". The all-cw atropoisomer of tetrakis(o-ami-nophenyl)porphyrin, as it was shown, gives complexes withchloride, bromide, nitráte, hydrogen sulfáte and dihydrogenphosphate .

The increasing interest in the design of guanidinium-basedreceptors arose from investigation of catalytic mechanism ofvarious enzymes (Fig. 5).

The guanidinium group is present in side chain of argininein enzymes that bind anionic substrates and is also involved inthe stabilization of protein tertiary structures via salt bridgeswith carboxylate function. Guanidine has an extremely highbasicity, which guarantees protonation in a very wide pH rangeand a very effective solvation in water. Several bis- andpolyguanidinium systems can form complexes with linear andcyclic phosphodiesters and mimic phosphodiesterase activi-ty (which was shown in imidazole-catalyzed mRNA hydroly-sis) . Enhanced preorganization of host was employed inthe design of a receptor for peptides. The 16-mer peptideswith two aspartate groups located at different positions alongthe chain were tested for binding with the receptor, whichwas arranged as a rigid scaffold to orient two guanidiniumgroups15.

In order to improve the binding characteristics, the gua-nidinium group can be embedded in a bicyclic framework.These bicyclic guanidinium groups formed ion pairs with a bignumber of anions3. They could be made also for the enantiose-lective recognition of amino acids, the catalysis, and specifictransport of substrates across membranes. The samé idea wasušed in the design of guanidinium nucleotide receptors. At-tachment of uracil and naphthoyl subunits to the host moleculeallows to get a receptor for adenine and the di- and oligonu-

cleotides . Another successful solution of tasks of anion rec-ognition has been realized in the idea of linking two chiralguanidinium moieties with a flexible spacer. Such host mole-cules can extract dicarboxylates (succinate or fumarate), butnot monocarboxylates, into the organic phase . The host hav-ing bulky silyl ether groups is capable of extracting oxoanionsfrom very dilute aqueous solutions. The highest preferencewas shown for sulfáte, but AMP2", ADP3", and ATP4" werealso extracted efficiently into the organic phase .

The introduction of a positive charge into organic frame-works as an alternativě to protonation can be very efficientlyaccomplished by metal cation ligation. In this way, receptorswith specifically designed coordination sites were construc-ted. When an organic chelating ligand binds to a metal cation,a mismatch of coordination sites may arise, which not neces-sarily spoils the complexation and may still give thermody-

Fig. 4. Protonated sapphyrins acts as a receptor for anionic guests

Fig. 5. A macrocyclic anion receptors containing guanidinium units

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namically stable species . For the formation of ion-pair thelower transition metal cations, notably Cu(I), Cu(II), Fe(II),Mn(II), Co(II), Ni(II), and Ru(II), háve been preferred, al-

Fig. 6. Metal functionalizcd hosts

though even the uranyl cation and the main group metals hávebeen successfully employed, and there is no obvious limitationto the use of elements from the entire range of periodic table.Anion binding in these systems is thus widespread. A numberof mono- and binuclear metallocomplexes on the basis ofbipyridines (cyclophanes), calixarenes, and cobalto- or ferro-cenes demonstrated binding affinity to a wide variety of anions(chloride, malonate, perchlorate, sulfáte, azide) * c(Fig. 6).

The calixarenes, cage-forming aromatic hosts, usuallybind metal cations or neutral organic guests. Their guestpreference can be inverted towards anions, providing that onlystrongly electron-attracting groups are attached to the aromaticrings (e.g. cations such as Ru2+, and Ir2+). Similar construc-tions can bind oxoanionic guests, like CF3SO'3, TcO;,, andCIO;2 (Ref.17).

The classic representatives of host compounds intendedfor molecular recognition in water are cyclodextrins4. Theyprovide toroidal cavities of variable size, and the guest mole-cules of correct complementary size can thus associate withthis class of host compounds. Many inorganic anions, such asCIO;, I", SCN", CH3COO", Cl", SOJ , form weak complexeswith cyclodextrins2. Modification of these hosts with imida-zole or pyridyl residues leads to intensification of their anion--binding characteristics. These modified cyclodextrins mayserve as hosts for a variety of organic anions such as pyro-catecholates, sulfonates, carboxylates, or nucleotides. Someof these compounds are capable of mimicking the features ofreál hydrolytic enzymes .

To the second group, according to mentioned classifica-tion, belong the electroneutral hosts for anions (Fig. 7).

The neutral anion binding receptors can be divided intotwo classes: receptors that bind anions exclusively by hydro-gen bonding or ion-dipole interactions, and receptors thatcoordinate anions as Lewis acidic centers of a neutral organo-metallic ligand a. Among the representatives of this group, areLewis acidic hosts connected by covalent bonds. At first, it is,e.g. boron Lewis acids, combined with naphthalene or crownether. Such a construction of a host molecule provides selec-tive binding of hydride and halide ions . Borane groups,replaced in macrocycles on trimethylsilyl moieties exhibited

OOC ^"-CCIO"

Fig. 7. Neutral receptors species for anion binding

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selectíve interaction with fluoride ion . Tin(IV)macrocyclesháve been characterized as capable of binding chloride anion .Organic tin(IV) compounds are known to possess an affinityto phosphate . A favorable candidate for use as an architec-tural element can be seen in mercury. It forms unusually stablecarbon bonds extending from the metal . With such macrocy-clic hosts, the halides complexes are easily formed2. TheLewis acidic hosts based on metal cation coordination alsobelong to this group. These are systems of neutral overallcharge. Tetranuclear Cu(I) complex, created on the basis ofrigid resorcinarene phosphonite ring, encapsulates chlorideguest anion2. A very similar complex was formed with Ag(I)--macrocycle and iodide. Large transition metal cations allowfor anchoring of the guests into an organic polychelate whileleaving still one coordination site open for additional bind-ing of a Lewis base . Complex Zn "^-A^-methylmesoporphyrinbinds yV-acyl-a -amino acid anions as guest species with strongenantioselectivity . Uranylsalenes (Fig. 8) displayed selecti-vity toward H 2 PO 4 (Ref. 3 a J 9). These host compounds we-re successfully tested as carriers in' experiments concerningtransport of phosphate anions across a supported liquid mem-brane2. Thus the utility and advantages of this design ofelectroneutral anion receptors was demonstrated.

Anion hosts operating by ion-dipole binding represents thethird group of artificial receptors family. Ion-dipole interac-tion has the samé dependence on the dielectric environment asthe interaction partners bearing full charges, but is consider-ably weaker on the absolute scale and decreases with thedistance more steeply2. Energy of the interaction of an ion anda dipóle depends on their mutual orientation. Hydrogen bondsare the most prominent representatives of dipolar elements andplay a very important role in biopolymers. They serve to"glue" host and guest together, especially in less polar sol-vents. As very helpful compounds in this čase can be viewedthe urea-base and flexible tentacle polyamine hosts, whichcomplexate with perchlorate, phosphate, carboxylate, and sul-fonate structures and with isosteric oxo-structures such aslactone and nitro ones2. Well-known and enjoying reputationas metal cation complexing agents are the calixarenes. Con-necting of the sulfonamide function to the upper rim of ca-lix[4]arene produced a host capable of distinguishing HSO4--ion from the chloride or nitráte , and joining tethered urea orthiourea moieties to calix[4]arene or calix[6]arene giving re-ceptors showed a strong and regioselective binding of the1,3,5-benzenetricarboxylate . Modification of calix[4]areneupper rim by urea moieties lead to effect of specific bind ofthe halide anions3b.

Calixpyrrole is a well-known and easily obtainable com-pound (Fig. 9).

It has been characterized as an electroneutral host withcone structure enabling to form cooperative hydrogen bondsof all pyrrole groups with the anionic guests. Calixpyrrole iscapable of binding fluoride with a strong preference overchloride or H 2 PO 4 (Ref.20). The neutral pentamethylpiperid-ine receptor also formed four amide-like hydrogen bond withcyclohexanedione enolate anion. A steroid-based macrocyclewas designed on this principle. It is capable of binding smallhalide anions .

Hydrogen bonding is sensitive to the accumulation ofnegative charge density and able to employ bond dipoles ofheavier, non-hydrogen elements . In order to make use of this

interaction principle, a macrocyclic tertiary amine containingfour borane-amine donor bonds was prepared . A large num-ber of inorganic anions were successfully complexed by thisborane-amine adduct. Similar anion-dipole interactions form-ed the basis of guest binding by macrocycle with sulfáte andphosphate centers23.

Electroneutral hosts can also arise from the compensationof equivalent numbers of full positive and negative charges.Adaptation of this principle for artificial receptors calls for thecreation of zwitterionic structures with distinct positive andnegative domains. Such zwitterionic compound were preparedby alkylation of the tertiary amine, showed extraordinarysolubility in water, and formed stable complexes with thehalides and cyanide2.

Application: separation processes, sensors(electrochemical, fluorescence)

Sensor technology has a long tradition. The chemicalsensors provide reliable information about their physical, che-mical and biological environments. Physical sensors, such asflow-meters, thermoelements and IR-position sensors, occupya key position in most innovate technical systems, whereas theapplication of chemical sensors has been limited to somespeciál areas. Supramolecular chemistry has a great potentialfor such possible applications. The quality of information

Fig. 8. Uranyl receptor for anionic guests combines Lewis aciditywith hydrogen bonds

Fig. 9. meso-Octametylcalix[4]pyrrole

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provided by chemical sensors is fundamentally different fromthat supplied by traditional analytical methods. In some cases,this has been the source of unexpected uncertainties in com-paring methods. Chemical sensors háve allowed the identifi-cation and quantification of specific species and háve hada great impact on the study of biological systems. Anionreceptors are now applied as the selector element in separationmembranes and in ion-selective electrodes. As one of suchuses the application of macrocyclic oligopyrrole compoundsare their use in molecular recognition for HPLC separation ofbiologically important anionic substrates can be mentioned .This application usually requires the immobilization of recep-tors on a polymeric matrix or silica gel. The covalent attach-ment of these receptors to a solid phase provides valuable toolfor understanding receptor-substrate interactions and givespossibility to determine the thermodynamic and kinetic factorsof particularbinding. The modification of silica-gel by attach-ment of receptor subunits can lead to the generation of supportsthat show differing affinities toward various anionic species40.Here, such suitable receptors as porphyrins, metalloporphy-rins, sapphyrins, calix[4]pyrroles and binaphthyl derivativeswere employed ' ' . These macrocycles (with carboxyl func-tions on the periphery) were bonded to aminopropyl-silica gel{via amide bonds) and then silylated. For comparison of theirseparation properties, bonded phases with various amounts ofmacrocyclic receptors were prepared . Separation modes arebased on hydrogen bond formation, axial ligand and coulom-bic interactions and 71-71 hydrophobic interactions.

Host-guest molecular recognition on membráně surfacesis a fundamental chemical process that controls many impor-tant biological reactions, such as antigen-antibody reactions,enzymatic reactions, carrier- or channel-mediated transport,and receptor reactions involving signál transduction. From theviewpoint of analytical chemistry, it gives important implica-tions for the sensing of target chemical substances ' . Animportant method for in šitu analysis of these substances isa measurement of the guest-induced membráně potentialchange. The ion-selective electrodes (ISE) are now beingintensi vely exploited. The electrode systém that is most widelyušed is a liquid membráně type, in which a lipophilic organicliquid membráně containing lipophilic host molecules is gene-rally supported by a póly vinyl chloride (PVC) polymer matrix.Forpractical applications different types of liquid membranes,námely bulk, supported, emulsion and polymer composite canbe ušed . Calix[4]pyrroles and metalloporphyrins with appen-ded cytosine unit were proposed as receptor of ion-selectiveelectrodes for nucleotide recognition . The molecular recog-nition of nucleotides is usually based on complementary basepairing, directed multiple hydrogen bonding, specific stack-ing, and generalized electrostatic interactions which act eitherindividually or cooperatively. The described receptors weredesigned as nucleotide receptors since the recognition processinvolves multiple binding interactions. It was found that mem-branes, containing substituted calix[4]pyrroles gave near-Nern-stian responses in the presence of both 5'-GMP and 5'-CMPand demonstrated the foliowing selectivities: 5'-AMP<5'--UMP<5'-TMP<5'-GMP<5'-CMP and 5'-AMP<5'-GMP<5'-UMP<5'-TMP<5'-CMP, respectively. On the other hand,the PVC-membranes based on cytosine-substituted metal-loporphyrins (Co(II) and Zn(II)) displayed high selectivityonly to 5'-CMP and similar selectivity to others nucleoside

monophosphates. In order to understand complex mechanismof binding between metalloporphyrins and nucleotide the un-substituted Co(II)-tetraphenylporphyrin háve been studied.Experimental data suggest that potentiometric response ofunsubstituted metalloporphyrin is controlled by both nucleo-bases coordination and phosphate chelation.

The most interesting aspect of the potentiometric selecti-vity appeared to be in the combination of Co(II)-porphyrin andlipophilic additive (such as tridodecylmethylammonium chlo-ride (TDMACÍ)). These results indicate, that cytosine-substi-tuted metalloporphyrin, and in particular the Co(II)-containingone, may be potentially useful for determination of comple-mentary nucleotide in the presence of 10 mol% TDMACÍ.

The open-chain and cyclic sapphyrin dimers bearing vari-ous bisamide spacers are also interesting as receptors for chiraldicarboxylate anions28. The chiral diamines should provide anadditional source of both hydrogen-bonding donor (i.e., NH)and acceptor (i.e., C = O) functionality that could complementthe "main" sapphyrin-to-carboxylate binding motif. In viewof this, (5)-2,2'-diamino-l,l'-binaphthalene and (1S,2S)-1,2--diaminocyclohexane as stereogenic linkers in these systemswere chosen. Chiral recognition of unprotected and protected(N-carbobenzyloxy, N-Cbz) aspartate and glutamate anionsby these compounds was examined by incorporating sap-phyrin-based receptors as active components into plasticizedPVC-membranes. Obtained data indicate, that enantioselec-tivity of the diaminocyclohexane-derived dimers toward glu-tamate is higher than that of the binaphthalene-containingreceptor, and that the enantioselectivity of both open-chainand cyclic dimers to N-Cbz-aspartate is controlled by plasti-cizer polarity.

Among ion-selective sensors capable of serving as carriersin the transfer of oxoanions to nonpolar organic phase, ruby-rin , lipophilic bis-guanidines , and macrotricyclic quaterna-ry ammoniumions RMQA +were described . The hosts pro-posed for the imitation of membráně transport exactly andselective transfer of halide and phosphate guests from the aque-ous environment to a PVC or phospholipide membráně phase.

Other electrochemical sensors, the aromatic boronic acids,interacted with O" and F" in solid matrices and organic so-lution . For electrochemical detection of fluoride ions inaqueous media ferrocenboronic acid3 2 was prepared. Chlorideions háve virtually no effect on the electrode potential, andneither háve thiocyanate, phosphate, sulfáte and others. Thecomplexation is caused by the strong Lewis acid - Lewisbase interaction. Hydroxide ions react, in analogy to fluorideion, with the boronic acid; but this occurs only in stronglyalkaline solutions and another redox reaction occurs in paral-lel. The ferroceneboronic acid has similar excellent selectivityas anion selective electrodes based on LaF3 but the principleis different32. Ferroceneboronic acid may find also industrialapplication as an inexpensive and highly selective sensor forfluoride anions. On the basis of others halide anions sensorsare cobaltocenium polyamide macrocyclic receptors, bis-co-baltocenium porphyrin- and calix[4]arene derivatives, or ca-lix[4]arene with Ru(II)-bipyridyl moiety, attached via amidebonds3b"c'33. They exhibit selectivity trend in the order Cl">B r " » N O 3 . A new class of anion selective receptors based onthe neutral uranylsalophene building block as Lewis acidicbinding site was described ' . Incorporation of these novelion receptors in PVC membranes on chemically modified field

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effect transistore (CHEMFETs) allow determination of pho-sphate and fluoride anions in aqueous solutions, even in pre-sence of anion excess of very lipophilic ions such as nitráteand perchlorate. CHEMFETs are silicon-based microsensorsthat can transduce the membráně potential of an ion selectivemembráně deposited on top of the semiconductor into anelectronic signál. The new series of uranilsalenes contained ofdifferent anion binding groups, like amides, urea moieties, andLewis acidic metal centers which combined both cation andanion binding properties also was proposed . These ditopicreceptors were tested for complexation studies of inorganicanions and can be applied as useful sensor element in poten-tiometric measurements.

Molecular recognition of such a natural póly anion as DNAwas recently shown on examples such as porphyrins andsapphyrins . The positively charged porphyrins and proto-nated expanded sapphyrins are capable of interacting withnucleic acids in several interesting ways. The main DNAbinding modes of porphyrins are electrostatic interaction bet-ween positively-charged substituents of porphyrins with thepolyanionic DNA sugar-phosphate backbone, the hydropho-bic interaction and intercalation. In the čase of sapphyrinsthree modes of the interaction with DNAs háve been found:phosphate anion chelation by the protonated core of sapphyrin,hydrophobic interaction, and at the low phosphate ester tosapphyrin ratios the formation of highly ordered aggrega-tion of sapphyrin on the surface of certain dsDNAs (Ref. ).Further progress in this area could provide novel polypyrro-le-conjugates with oligonucleotides . The macrocyclic unitsattached to an oligonucleotide can serve a duál role: it can actas a sequence-specific modification agent and also increasethe affinity of a macrocyclic-bearing oligonucleotide to a com-plementary sequence.

Compounds incorporating a binding site and a fluoro-phore, and which dispose of a mechanism for communicationbetween the host and guest, are called fluorescent chemosen-sors38. These sensing molecules contain the bipyridyl, naph-thalene, anthracene or acridine cores, attached via polyaminemoieties. Such receptors háve the potential to give a highlysensitive light-emitting response on complexation of a largerange of organic anions (including such polyanions as DNAor heparin) . Binding selectivities of fluorogenic chemosen-sors, combined with their photophysical properties, offer at-tractive features for its use as fluorescent sensors for thedetection of anions and polyanions, especially in the čase ofbiological targets involving nucleic acids .

Conclusion

The anion receptors are very diverse as to their chemicalnature, ranging from macromolecular proteins to relativelylow molecular synthetic macrocycles. The structures of anionbinding sites in the molecules, as well as binding modes, arealso highly different. A lot of anion hosts are able to bindbiologically important anions in anion enzyme-mimic man-ner. Their features are very useful in a variety of applications.Among the anion carriers háve found a particularly wide fieldof application as components in anion-selective membra-ne electrodes, e.g. in clinical chemistry (solvent polymericmembráně electrodes) or electrophysiology (microelec-

trodes) ' , as detectors in ion chromatography , in highlyselective transport processes through artificial and biologicalmembranes. As a result of the introduction of synthetic iono-phores as anion-selective components in membráně basedsensor systems of analytically relevant selectivity, the directmeasurement of Cl", COf" N O 2 , NOj , C1O4, NCS", HCOj,BF4 has become available . The direct extra- and intra-cellu-lar measurement of Cl", NOj, and CO§" háve also been ren-dered possible with neutral ionophore-based microelectro-des4 3 ' . The study of anion supramolecules and their deriva-tives has been fruitful in a number of various new macrocyclesproduced. The study of the interaction of these new hosts witha variety of guests has opened many ways of research and hasled to a number of promising applications.

Financial support from the Czech grant agency (grant No.203/96/0740 and No. 203/97/1099) and Ministry ofEducation(grant No. VS 97 135) is gratefully acknowledged.

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V. Král, O. Rusin, T. Shishkanova, R. Volf, P. Matějka,and K. Volka (Department of Analytical Chemistry, Instituteof Chemical Technology, Prague): Anion Binding: FromSupramolecules to Sensors

The article deals with the recent synthesis of a host ofreagents for anion and polyanion binding and describes thewhole area of use ranging from analytical chemistry andenvironmental science to medicinal applications.

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anion binding: from supramolecules to sensors · phosphate anions through cell membranes is also...

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